Capture verification for cardiac resynchronization pacing optimization

ABSTRACT

A system and method for automatically selecting among a plurality of pacing modes based upon capture detection. Patients suffering from heart failure may be optimally treated with different resynchronization pacing modes or configurations. By detecting whether capture is being achieved by a particular configuration or mode, a device is able to automatically switch to one that is both optimal in treating the patient and is successful in capturing the heart with pacing pulses.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.09/999,255, filed on Oct. 31, 2001, the specification of which isincorporated herein by reference.

FIELD OF THE INVENTION

This patent application pertains to methods and apparatus for cardiacrhythm management. In particular, it relates to methods and apparatusfor providing cardiac resynchronization therapy.

BACKGROUND

Cardiac rhythm management devices are implantable devices that provideelectrical stimulation to selected chambers of the heart in order totreat disorders of cardiac rhythm. A pacemaker, for example, is acardiac rhythm management device that paces the heart with timed pacingpulses. The most common condition for which pacemakers are used is inthe treatment of bradycardia, where the ventricular rate is too slow.Atrio-ventricular conduction defects (i.e., AV block) that are permanentor intermittent and sick sinus syndrome represent the most common causesof bradycardia for which permanent pacing may be indicated. Iffunctioning properly, the pacemaker makes up for the heart's inabilityto pace itself at an appropriate rhythm in order to meet metabolicdemand by enforcing a minimum heart rate.

Pacing therapy can also be used in the treatment of congestive heartfailure (CHF), which is a clinical syndrome in which an abnormality ofcardiac function causes cardiac output to fall below a level adequate tomeet metabolic demand. CHF can be due to a variety of etiologies withthat due to ischemic heart disease being the most common. Some CHFpatients suffer from some degree of AV block or are chronotropicallydeficient such that their cardiac output can be improved withconventional bradycardia pacing. It has also been shown, however, thatsome CHF patients suffer from intraventricular and/or interventricularconduction defects (e.g., bundle branch blocks) such that their cardiacoutputs can be increased by improving the synchronization of ventricularcontractions with electrical stimulation. Other conduction defects canoccur in the atria. Cardiac rhythm management devices have thereforebeen developed which provide electrical stimulation to the atria and/orventricles in an attempt to improve the coordination of cardiaccontractions, termed cardiac resynchronization therapy.

SUMMARY OF THE INVENTION

The present invention is a method and system for automaticallyoptimizing the operation of a cardiac rhythm management device basedupon verification of capture during device operation. In accordance withthe invention, pacing pulses are output through selected pacing channelsmaking up a selected pacing configuration in accordance with aprogrammed pacing mode associated with the selected pacingconfiguration. A capture verification test is performed at a selectedtime to test a selected sensing/pacing channel for presence or loss ofcapture during a pacing pulse, the capture verification test beingperformed by sensing whether an evoked response occurs during a capturedetection window following the output of a pacing pulse. Upon detectionof a loss of capture in a pacing channel making up the selected pacingconfiguration, the device switches from the selected pacingconfiguration and associated pacing mode to a next pacing configurationand associated pacing mode contained in an ordered list. The pacingconfigurations and associated modes in the ordered list may be ranked inorder of therapeutic benefit as determined by clinical testing of aparticular patient. In one embodiment, upon detection of a loss ofcapture in a pacing channel, a next pacing configuration and associatedpacing mode that does not employ the pacing channel in which a loss ofcapture was detected is selected from the ordered list. The list ofpacing configurations and associated pacing modes may include, forexample, a biventricular pacing configuration, a left ventricular-onlypacing configuration, a right ventricular-only pacing configuration, anda configuration in which no pacing is performed. The pacing modeassociated with each pacing configuration may include various pacingparameters such as an AV delay interval employed in atrial trackingand/or sequential atrio-ventricular pacing modes.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a system diagram of a pacemaker configured for biventricularpacing and sensing.

FIG. 2 illustrates an exemplary switching circuit.

FIGS. 3A and 3B show data obtained from two exemplary patients thatillustrate the hemodynamic effects of different AV delay intervals withdifferent pacing configurations.

DETAILED DESCRIPTION

Cardiac rhythm management devices for delivering resynchronizationtherapy may be configured in a number of different ways and with anumber of different parameter settings. The effectiveness of aparticular configuration and parameter set, however, depends upon theextent to which the resynchronization pacing pulses are achievingcapture of the heart. As described below, a device may be configured totest whether capture is being achieved and modify its operationaccordingly.

1. Hardware Platform

Pacemakers are typically implanted subcutaneously or submuscularly in apatient's chest and have leads threaded intravenously into the heart toconnect the device to electrodes used for sensing and pacing. Leads mayalso be positioned on the epicardium by various means. A programmableelectronic controller causes the pacing pulses to be output in responseto lapsed time intervals and sensed electrical activity (i.e., intrinsicheart beats not as a result of a pacing pulse). Pacemakers senseintrinsic cardiac electrical activity by means of internal electrodesdisposed near the chamber to be sensed. A depolarization wave associatedwith an intrinsic contraction of the atria or ventricles that isdetected by the pacemaker is referred to as an atrial sense orventricular sense, respectively. In order to cause such a contraction inthe absence of an intrinsic beat, a pacing pulse (either an atrial paceor a ventricular pace) with energy above a certain pacing threshold isdelivered to the chamber.

A block diagram of a multi-site pacemaker having three sensing/pacingchannels is shown in FIG. 1. (As the term is used herein, a “pacemaker”should be taken to mean any cardiac rhythm management device, such as animplantable cardioverter/defibrillator, with a pacing functionality.)The controller of the pacemaker is made up of a microprocessor 10communicating with a memory 12 via a bidirectional data bus, where thememory 12 comprises a ROM (read-only memory) for program storage and aRAM (random-access memory) for data storage. The controller can beimplemented by other types of logic circuitry (e.g., discrete componentsor programmable logic arrays) using a state machine type of design, buta microprocessor-based system is preferable. The controller is capableof operating the pacemaker in a number of programmed modes where aprogrammed mode defines how pacing pulses are output in response tosensed events and expiration of time intervals. A telemetry interface 80is also provided for communicating with an external programmer.

The multiple sensing/pacing channels may be configured to deliverbiventricular pacing, biatrial pacing, or multi-site pacing of a singlechamber. Illustrated in FIG. 1 is a configuration with one atrial andtwo ventricular sensing/pacing channels for delivering biventricularpacing. The atrial sensing/pacing channel in FIG. 1 comprises ringelectrode 43 a, tip electrode 43 b, sense amplifier 41, pulse generator42, and an atrial channel interface 40 which communicatesbidirectionally with a port of microprocessor 10. The device also hastwo ventricular sensing/pacing channels that similarly include ringelectrodes 23 a and 33 b, tip electrodes 23 b and 33 b, sense amplifiers21 and 31, pulse generators 22 and 32, and ventricular channelinterfaces 20 and 30. Incorporated into each sensing/pacing channel isthus a pacing channel made up of the pulse generator connected to theelectrode and a sensing channel made up of the sense amplifier connectedto the electrode. The electrodes are electrically connected to thedevice by means of a lead. For each channel, the same lead and electrodeare used for both sensing and pacing. The pacemaker also has an evokedresponse sensing channel that comprises an evoked response channelinterface 50 and a sense amplifier 51. The channel interfaces includeanalog-to-digital converters for digitizing sensing signal inputs fromthe sensing amplifiers, registers that can be written to for adjustingthe gain and threshold values of the sensing amplifiers, and, in thecase of the ventricular and atrial channel interfaces, registers forcontrolling the output of pacing pulses and/or changing the pacing pulseamplitude.

The controller 10 controls the overall operation of the device inaccordance with programmed instructions stored in memory, includingcontrolling the delivery of paces via the pacing channels, interpretingsense signals received from the sensing channels, and implementingtimers for defining escape intervals and sensory refractory periods. Thesensing circuitry of the pacemaker detects a chamber sense, either anatrial sense or ventricular sense, when a sense signal (i.e., a voltagesensed by an electrode representing cardiac electrical activity,sometimes called an electrogram signal) generated by a particularchannel exceeds a specified intrinsic detection threshold. Pacingalgorithms used in particular pacing modes employ such senses to triggeror inhibit pacing. Both the pacing mode and the pacing configuration,which specifies which of the available pacing channels in a device areto be used to deliver paces, are implemented by appropriate programmingof the controller.

2. Bradycardia Pacing Modes

Bradycardia pacing modes refer to pacing algorithms used to pace theatria and/or ventricles when the intrinsic atrial and/or ventricularrate is inadequate due to, for example, AV conduction blocks or sinusnode dysfunction. Such modes may either be single-chamber pacing, whereeither an atrium or a ventricle is paced, or dual-chamber pacing inwhich both an atrium and a ventricle are paced. The modes are generallydesignated by a letter code of three positions where each letter in thecode refers to a specific function of the pacemaker. The first letterrefers to which heart chambers are paced and which may be an A (foratrium), a V (for ventricle), D (for both chambers), or 0 (for none).The second letter refers to which chambers are sensed by the pacemaker'ssensing channels and uses the same letter designations as used forpacing. The third letter refers to the pacemaker's response to a sensedP wave from the atrium or an R wave from the ventricle and may be an I(for inhibited), T (for triggered), D (for dual in which both triggeringand inhibition are used), and O (for no response). Modern pacemakers aretypically programmable so that they can operate in any mode which thephysical configuration of the device will allow. Additional sensing ofphysiological data allows some pacemakers to change the rate at whichthey pace the heart in accordance with some parameter correlated tometabolic demand. Such pacemakers are called rate-adaptive pacemakersand are designated by a fourth letter added to the three-letter code, R.

Pacemakers can enforce a minimum heart rate either asynchronously orsynchronously. In asynchronous pacing, the heart is paced at a fixedrate irrespective of intrinsic cardiac activity. There is thus a riskwith asynchronous pacing that a pacing pulse will be deliveredcoincident with an intrinsic beat and during the heart's vulnerableperiod which may cause fibrillation. Most pacemakers for treatingbradycardia today are therefore programmed to operate synchronously in aso-called demand mode where sensed cardiac events occurring within adefined interval either trigger or inhibit a pacing pulse. Inhibiteddemand pacing modes utilize escape intervals to control pacing inaccordance with sensed intrinsic activity. In an inhibited demand mode,a pacing pulse is delivered to a heart chamber during a cardiac cycleonly after expiration of a defined escape interval during which nointrinsic beat by the chamber is detected. If an intrinsic beat occursduring this interval, the heart is thus allowed to “escape” from pacingby the pacemaker. Such an escape interval can be defined for each pacedchamber. For example, a ventricular escape interval can be definedbetween ventricular events so as to be restarted with each ventricularsense or pace. The inverse of this escape interval is the minimum rateat which the pacemaker will allow the ventricles to beat, sometimesreferred to as the lower rate limit (LRL).

In atrial tracking pacemakers (i.e., VDD or DDD mode), anotherventricular escape interval is defined between atrial and ventricularevents, referred to as the atrio-ventricular interval (AVI). Theatrio-ventricular interval is triggered by an atrial sense or pace andstopped by a ventricular sense or pace. A ventricular pace is deliveredupon expiration of the atrio-ventricular interval if no ventricularsense occurs before. Atrial-tracking ventricular pacing attempts tomaintain the atrio-ventricular synchrony occurring with physiologicalbeats whereby atrial contractions augment diastolic filling of theventricles. If a patient has a physiologically normal atrial rhythm,atrial-tracking pacing also allows the ventricular pacing rate to beresponsive to the metabolic needs of the body.

A pacemaker can also be configured to pace the atria on an inhibiteddemand basis. An atrial escape interval is then defined as the maximumtime interval in which an atrial sense must be detected after aventricular sense or pace before an atrial pace will be delivered. Whenatrial inhibited demand pacing is combined with atrial-triggeredventricular demand pacing (i.e., DDD mode), the lower rate limitinterval is then the sum of the atrial escape interval and theatrio-ventricular interval.

Another type of synchronous pacing is atrial-triggered orventricular-triggered pacing. In this mode, an atrium or ventricle ispaced immediately after an intrinsic beat is detected in the respectivechamber. Triggered pacing of a heart chamber is normally combined withinhibited demand pacing so that a pace is also delivered upon expirationof an escape interval in which no intrinsic beat occurs. Such triggeredpacing may be employed as a safer alternative to asynchronous pacingwhen, due to far-field sensing of electromagnetic interference fromexternal sources or skeletal muscle, false inhibition of pacing pulsesis a problem. If a sense in the chamber's sensing channel is an actualdepolarization and not a far-field sense, the triggered pace isdelivered during the chamber's physiological refractory period and is ofno consequence.

3. Cardiac Resynchronization Therapy

Cardiac resynchronization therapy is pacing stimulation applied to oneor more heart chambers in a manner that restores or maintainssynchronized contractions of the atria and/or ventricles and therebyimproves pumping efficiency. Certain patients with conductionabnormalities may experience improved cardiac synchronization withconventional single-chamber or dual-chamber pacing as described above.For example, a patient with left bundle branch block may have a morecoordinated contraction of the ventricles with a pace than as a resultof an intrinsic contraction. Resynchronization pacing, however, may alsoinvolve delivering paces to multiple sites of a heart chamber or pacingboth ventricles and/or both atria in accordance with a resynchronizationpacing mode as described below. Ventricular resynchronization pacing isuseful in treating heart failure because, although not directlyionotropic, resynchronization results in a more coordinated contractionof the ventricles with improved pumping efficiency and increased cardiacoutput. Resynchronization pacing of the atria may also be beneficial incertain heart failure patients, particularly for preventing the onset ofatrial arrhythmias.

One way to deliver resynchronization therapy is to pace a site with asynchronous bradycardia pacing mode and then deliver one or moreresynchronization paces to one or more additional pacing sites in adefined time relation to one or more selected sensing and pacing eventsthat either reset escape intervals or trigger paces in the bradycardiapacing mode. One such resynchronization pacing mode may be termed offsetresynchronization pacing. In this mode, a first site is paced with abradycardia mode, and a second site receives a resynchronization pace atan offset interval with respect to the pace delivered to the first site.The offset interval may be zero in order to pace both sitessimultaneously, positive in order to pace the first site after thesecond, or negative to pace the first site before the second. Forexample, in biventricular resynchronization pacing, one ventricle ispaced with a bradycardia mode while the contralateral ventricle receivesresynchronization paces at the specified biventricular offset interval.The offset interval would normally be individually specified to optimizecardiac output in a particular patient. Ventricular resynchronizationcan also be achieved in certain patients by pacing at a singleunconventional site, such as the left ventricle instead of the rightventricle. In such a mode, right ventricular senses may be used totrigger left ventricular paces or used to define an escape interval thatupon expiration causes delivery of a left ventricular pace.

4. Capture Verification

In order for a pacemaker to control the heart rate and/or enhancepumping efficiency in the manner described above, the paces delivered bythe device must achieve “capture,” which refers to causing sufficientdepolarization of the myocardium that a propagating wave of excitationand contraction result (i.e., a heart beat). A pacing pulse that doesnot capture the heart is thus an ineffective pulse. This not only wastesenergy from the limited energy resources (battery) of pacemaker, but canhave deleterious physiological effects as well, since a pacemaker thatis not achieving capture is not performing its function in enforcing aminimum heart rate in the case of bradycardia pacing, or insynchronizing cardiac contractions in the case of resynchronizationtherapy. A number of factors can determine whether a given pacing pulsewill achieve capture including the energy of the pulse, which is afunction of the pulse's amplitude and duration or width, and theintegrity and physical disposition of the pacing lead.

A common technique used to determine if capture is present during agiven cardiac cycle is to look for an “evoked response” immediatelyfollowing a pacing pulse. The evoked response is the wave ofdepolarization that results from the pacing pulse and evidences that thepaced chamber has responded appropriately and contracted. By detectingthe evoked P-wave or evoked R-wave, the pacemaker is able to detectwhether the pacing pulse (A-pulse or V-pulse) was effective in capturingthe heart, that is, causing a contraction in the respective heartchamber. In order for a pacemaker to detect whether an evoked P-wave oran evoked R-wave occurs immediately following an A-pulse or a V-pulse, aperiod of time, referred to as the atrial capture detection window orthe ventricular capture detection window, respectively, starts after thegeneration of the pulse. Sensing channels are normally renderedrefractory (i.e., insensitive) for a specified time period immediatelyfollowing a pace in order to prevent the pacemaker from mistaking apacing pulse or afterpotential for an intrinsic beat. This is done bythe pacemaker controller ignoring sensed events during the refractoryintervals, which are defined for both atrial and ventricular sensingchannels and with respect to both atrial and ventricular pacing events.Furthermore, a separate period that overlaps the early part of arefractory interval is also defined, called a blanking interval duringwhich the sense amplifiers are blocked from receiving input in order toprevent their saturation during a pacing pulse. If the same sensingchannels are used for both sensing intrinsic activity and evokedresponses, the capture detection window must therefore be defined as aperiod that supercedes the normal refractory period so that the sensingcircuitry within the pacemaker becomes sensitive to an evoked P-wave orR-wave.

Capture verification can be performed by delivering a pacing pulse andattempting to sense an evoked response during the capture detectionwindow through an evoked response sensing channel which may be either achannel normally used for sensing intrinsic activity or a dedicatedchannel. In an exemplary embodiment, a capture verification test isperformed by a multi-site pacemaker such as shown in FIG. 1 using adedicated evoked response sensing channel. In this test, it isdetermined whether or not a sensing/pacing channel is achieving capturewith the pacing pulses delivered by the channel's electrode. The evokedresponse sensing channel includes a sense amplifier for sensing anevoked response generated after a pacing pulse is delivered. The evokedresponse sensing channel is connected to a selected electrode of thepacemaker's sensing/pacing channels by means of a switching circuit.After switching the input of the evoked response sensing channel to theelectrode that is to be tested to verify capture and the delivery of apacing pulse, an evoked response is either detected or not by comparingthe output of the sensing amplifier to a specified evoked responsedetection threshold, thus signifying the presence or loss of capture,respectively. Although the same electrode can be used for pacing andevoked response detection during a capture verification test, the inputof the evoked response sensing channel preferably is switched to anelectrode of another sensing/pacing channel. The particular electrodeused for evoked response detection can be selected in accordance withwhich electrode is placed in a location where an evoked response due tothe pacing electrode can be most easily sensed. The sense amplifier ofthe evoked response sensing channel is then blanked during the captureverification test for a specified blanking period following a pacingpulse output by the tested sensing/pacing channel. The blanking periodis followed by a capture detection window during which an evokedresponse may be sensed by the evoked response sensing channel. In anexemplary embodiment, the blanking period may be approximately 10 ms,and the width of the capture detection window may range from 50 to 350ms.

Referring back to FIG. 1, the electrodes are connected to the senseamplifiers by means of a switching circuit 70 which enables theamplifiers to be connected to selected tip or ring electrodes of any ofthe sensing/pacing channels that connect through the switching circuit70. Each sense amplifier amplifies the voltage difference between twoinputs, and the inputs may be selected from any of the tip or ringelectrodes or the pacemaker case or can 60, which is also electricallyconnected to the switching circuit. The configuration of the switchingcircuit 70 is preferably implemented as an array of MOSFET transistorscontrolled by outputs of the controller 10. FIG. 2 shows a portion of abasic exemplary switching circuit. In this circuit, a pair of MOSFETtransistors Q1 and Q2 along with inverter INV form a double-pole switchthat switches one of the inputs to amplifier 51 between ring electrode23 a and 33 a. The other input is shown as being connected to can 60,but in other embodiments it may also be switched to one of theelectrodes by means of the switching circuit. In a more complicatedversion of the same basic pattern, the switching circuit 70 may be ableto switch the inputs of the evoked response sensing channel to any ofthe tip or ring electrodes of the sensing/pacing channels or to the can60.

5. Automatic Selection of Pacing Configuration

Cardiac rhythm management devices for resynchronization pacing canoperate in a number of pacing configurations that specify the locationand number of pacing sites. Each such pacing configuration employs aparticular pacing mode that specifies how pacing pulses are to be outputin response to lapsed time intervals and sensed events. A pacing modealso includes various parameter settings such as the AV delay intervalfor atrial tracking and/or atrio-ventricular sequential pacing modes.For a given patient, different combinations of pacing configurations andmodes may yield differing degrees of therapeutic benefit. Clinicaltesting of the patient while the device is operating is commonlyemployed to select a particular pacing configuration and mode that isoptimum for that particular patient. A parameter commonly used inoptimizing ventricular resynchronization pacing is the maximum rate ofsystolic pressure rise in the left ventricle, referred to herein as theLV max dP/dt. The LV max dP/dt can be measured with a Swan-Ganz catheterand is commonly used as a surrogate for myocardial contractility.Ventricular resynchronization pacing that increases the LV max dP/dtparameter can be assumed to be effective in restoring coordination ofventricles that has been lessened by conduction defects and inincreasing cardiac output.

In accordance with the invention, the controller of a pacemaker such asillustrated in FIG. 1 is programmed to pace the heart with a particularpacing configuration and associated pacing mode, where a pacingconfiguration is made up of selected pacing channels that the controlleruses to output pacing pulses by operating the pulse generator of thatchannel. The pacemaker controller is also programmed to perform captureverification testing at selected times in order to test a selectedsensing/pacing channel for presence or loss of capture during a pacingpulse. As explained above, the capture verification test is performed bysensing whether an evoked response occurs during a capture detectionwindow following the output of a pacing pulse. A loss of captureoccurring in a pacing channel can be due, for example, to leaddislodgement or exit block at the electrode. When such a loss of captureoccurs in a pacing channel, the selected pacing configuration iscompromised and is no longer delivering optimal therapy to the patient.One alternative when this happens is to simply continue pacing with thesame pacing mode even though the pacing configuration has beeneffectively altered by one of the sensing/pacing channels failing toreliably achieve capture. This may not be the most therapeuticallybeneficial pacing mode for the patient, however, since different pacingconfigurations may require different pacing modes in order to delivertherapy optimally. In accordance with the invention, the controller isprogrammed with an ordered list containing different pacingconfigurations and associated pacing modes. At any point in time, onesuch pacing configuration and mode is selected for use by the device indelivering pacing therapy to the patient. Upon detection of a loss ofcapture in a sensing/pacing channel making up the selected pacingconfiguration, the controller is programmed to switch from the selectedpacing configuration and associated pacing mode to a next pacingconfiguration and associated pacing mode contained in the ordered list.A pacing configuration and mode combination in the list may either bemade up of one or more selected sensing/pacing channels and anassociated mode that includes one or more parameter settings or mayconstitute no pacing at all.

The pacing configurations and associated modes in the ordered list maybe ranked in order of therapeutic benefit as determined by clinicaltesting of a particular patient. Such testing may either be performed bymeasuring the LV max dP/dt parameter or other parameters that have beenshown to reflect the hemodynamic effects of resynchronization therapy.The controller may also be programmed to select a next pacingconfiguration and associated pacing mode from the ordered list that doesnot employ a sensing/pacing channel in which a loss of capture wasdetected. For example, if a loss of capture occurs in two or more pacingchannels of a multi-site pacemaker, the controller may skip down thelist until a pacing configuration is found that does not employ thosechannels.

The capture verification tests on the pacing channels may be performedusing an evoked response sensing channel which may either be a dedicatedchannel or a channel normally used for other purposes. The test may beperformed for each pacing pulse output through a particular channel orat periodic or otherwise selected times. Also, detection of capture lossmay constitute one instance of a failure of the capture verificationtest or may constitute a preset number of such failures. By requiringmore than one instances of capture verification failure in a channelbefore a loss of capture is deemed to have been detected, switching ofthe pacing configuration is avoided when a spurious loss of capture in achannel occurs that may not happen again.

In an exemplary embodiment, a pacemaker is equipped as illustrated inFIG. 1 with two ventricular sensing/pacing channels and one atrialsensing/pacing channel and programmed to deliver ventricularresynchronization therapy with pacing configurations that include bothventricles, the right ventricle only, or the left ventricle only. Eachsuch pacing configuration has an associated atrial tracking and/orsequential atrio-ventricular pacing mode with a particular AV delayinterval setting. FIGS. 3A and 3B show data obtained from two examplepatients during clinical testing of the device using the three pacingconfigurations with different settings of the AV delay interval. Eachdata point of the figures represents either a biventricular (BV), leftventricle-only (LV), or right ventricle-only (RV) pacing configurationand shows the percent difference in LV max dP/dt for a given AV delayinterval.

FIG. 3A shows that, for this particular patient, the mosttherapeutically beneficial pacing configuration and mode combination isBV pacing with an AV delay interval of 65 milliseconds. For RV pacing,the optimum AV delay interval is also 65 milliseconds. For the LV pacingconfiguration, however, the optimum AV interval is 130 milliseconds. Anordered list of the pacing configurations and modes ranked according totherapeutic benefit would then be:

-   -   1. BV pacing with an AV delay interval of 65 milliseconds    -   2. LV pacing with an AV delay interval of 130 milliseconds    -   3. RV pacing with an AV delay interval of 65 milliseconds        The device can thus be initially programmed to operate with BV        pacing and an AV delay of 65 milliseconds. If a loss of capture        occurs in the left ventricular sensing/pacing channel, the next        pacing configuration that does not include that channel is RV        pacing also with an AV delay of 65 milliseconds. The device        would effectively revert to this even if no pacing configuration        and mode switching were to be performed by the device since the        left ventricular pacing channel is failing to capture the heart.        If a loss of capture occurs in the right ventricular channel,        however, the next most therapeutically beneficial pacing        configuration and mode combination that does not include the        right ventricular channel is LV pacing with an AV delay interval        of 130 milliseconds. If no pacing configuration and mode        switching in accordance with the invention were performed in        this instance, the device would revert to LV pacing but the AV        delay interval would still be 65 milliseconds. As shown in FIG.        3A, such a pacing configuration and mode combination would be        significantly suboptimal for this particular patient.

FIG. 3B shows data for another example patient and shows that the mosttherapeutically beneficial pacing configuration and mode combination iseither BV pacing with an AV delay interval of 150 milliseconds or LVpacing also with an AV delay interval of 150 milliseconds. For the RVpacing configuration, however, the optimum AV interval is 80milliseconds. An ordered list of the pacing configurations and modesranked according to therapeutic benefit would then be:

-   -   1. BV or LV pacing with an AV delay interval of 150 milliseconds    -   2. RV pacing with an AV delay interval of 80 milliseconds        If a pacemaker were operating in this patient with BV pacing and        an AV delay interval of 150 milliseconds, and a loss of capture        were to occur in the LV channel, the device would effectively        revert to RV pacing with an AV delay interval of 150        milliseconds if no mode switching is employed. A more        therapeutically beneficial result is obtained, however, by        switching to the next configuration and mode combination in the        list so that the AV delay interval is decreased to 80        milliseconds.

As described above, optimization of the pacing configuration and modeafter detection of a loss of capture in a particular channel may beaccomplished with an ordered list where various combinations of pacingconfigurations and mode parameter settings are ranked according to theresults of clinical testing. Such ordered lists can be created initiallyfor a particular patient and then updated periodically when follow-uptesting is performed. In another embodiment, a cardiac rhythm managementdevice is programmed to optimize one or more pacing mode parametersetting as a result of tests performed by the device itself. Forexample, a device may incorporate a pressure sensor 500 for detectingleft ventricular pressure as shown in FIG. 1. Upon detection of a lossof capture in a particular sensing/pacing channel, the device may thenre-optimize the AV delay interval with the residual pacing configurationbased upon left-ventricular pressure measurements such as the LV maxdP/dt or pulse pressure. Alternatively, if the patient ischronotropically competent, the baroreceptor reflex that controls theatrial rate may be employed to optimize the AV delay interval byselecting the interval that maximizes the atrial cycle length.

Although the invention has been described in conjunction with theforegoing specific embodiments, many alternatives, variations, andmodifications will be apparent to those of ordinary skill in the art.Such alternatives, variations, and modifications are intended to fallwithin the scope of the following appended claims.

1. A cardiac rhythm management device, comprising: one or more sensingchannels, each channel comprising an electrode connected to a senseamplifier for generating sense signals representing cardiac electricalactivity; a plurality of pacing channels, each channel comprising anelectrode adapted for disposition at a selected ventricular pacing site;a controller for controlling the delivery of pacing pulses by a selectedfirst pacing configuration to multiple ventricular sites in accordancewith a programmed atrial tracking and/or sequential atrio-ventricularpacing mode which includes a selected AV delay interval; and, whereinthe controller is programmed to: perform a capture verification test ata selected time to test a selected ventricular pacing channel forpresence or loss of capture during a pacing pulse, the captureverification test being performed by detecting whether an evokedresponse occurs during a capture detection window following the outputof a pacing pulse; and, upon detection of a loss of capture in a pacingchannel, re-optimize the AV delay interval for a residual second pacingconfiguration which does not include the pacing channel in which loss ofcapture was detected.
 2. The device of claim 1 further comprising: anevoked response sensing channel for detecting an evoked responsegenerated after a pacing pulse; and, a switching circuit for switchingthe input of the evoked response sensing channel to a selected electrodeof a pacing channel.
 3. The device of claim 1 wherein the selected firstpacing configuration is biventricular pacing.
 4. The device of claim 3wherein the residual second pacing configuration is right ventricle-onlypacing.
 5. The device of claim 3 wherein the residual second pacingconfiguration is left ventricle-only pacing.
 6. The device of claim 1wherein the selected first pacing configuration is multi-site pacing ofa single ventricle.
 7. The device of claim 1 wherein the controller isprogrammed to re-optimize the AV delay interval by selecting the AVdelay interval that maximizes the atrial cycle length.
 8. The device ofclaim 1 further comprising a pressure sensor and wherein the controlleris programmed to re-optimize the AV delay interval based upon pressuremeasurements.
 9. The device of claim 8 wherein the controller isprogrammed to re-optimize the AV delay interval based uponleft-ventricular pulse pressure measurements.
 10. The device of claim 8wherein the controller is programmed to re-optimize the AV delayinterval based upon the maximum rate of systolic pressure rise in theleft ventricle, referred to as the LV max dP/dt.
 11. A method foroperating a cardiac rhythm management device, comprising: generatingsense signals corresponding to cardiac electrical activity through oneor more sensing channels; outputting pacing pulses through multipleventricular pacing channels making up a selected first pacingconfiguration in accordance with a programmed atrial tracking and/orsequential atrio-ventricular pacing mode which includes a selected AVdelay interval; performing a capture verification test at a selectedtime to test a selected pacing channel for presence or loss of captureduring a pacing pulse, the capture verification test being performed bydetecting or not detecting an evoked response during a capture detectionwindow following the output of a pacing pulse; and, upon detection of aloss of capture in a pacing channel, re-optimizing the AV delay intervalfor a residual second pacing configuration which does not include thepacing channel in which loss of capture was detected.
 12. The method ofclaim 11 further comprising: detecting an evoked response generatedafter a pacing pulse through an evoked response sensing channel; and,switching the input of the evoked response sensing channel to a selectedelectrode of a pacing channel.
 13. The method of claim 11 wherein theselected first pacing configuration is biventricular pacing.
 14. Themethod of claim 13 wherein the residual second pacing configuration isright ventricle-only pacing.
 15. The method of claim 13 wherein theresidual second pacing configuration is left ventricle-only pacing. 16.The method of claim 111 wherein the selected first pacing configurationis multi-site pacing of a single ventricle.
 17. The method of claim 11further comprising re-optimizing the AV delay interval by selecting theAV delay interval that maximizes the atrial cycle length.
 18. The methodof claim 11 further comprising re-optimizing the AV delay interval basedupon pressure measurements.
 19. The method of claim 18 furthercomprising re-optimizing the AV delay interval based uponleft-ventricular pulse pressure measurements.
 20. The method of claim 18further comprising re-optimizing the AV delay interval based upon themaximum rate of systolic pressure rise in the left ventricle, referredto as the LV max dP/dt.